The results of the SURMOUNT-4 study were published in the Dec. 11 issue of the Journal of the American Medical Association and were sponsored by Eli Lilly. The findings suggest that the drug can greatly help those with weight-related health problems, but it is not a quick fix for weight loss.
"Obesity is a major driver of many of the conditions we spend our time treating in medicine; Conditions such as high blood pressure, heart disease, diabetes, and fatty liver are either caused by or exacerbated by obesity, "said lead study author Louis Aronne, PhD, the Sanford I. Weill Professor of Metabolic Research and director of the Comprehensive Weight Control Center, part of the Division of Endocrinology, Diabetes, and Metabolism at Weill Cornell Medical College. "The fact that we now have effective drugs is exciting and beneficial."
Diabetes drugs promote weight loss
Ticetide is part of a new class of drugs known as GLP-1 receptor agonists, which are being developed to treat type 2 diabetes. In addition to controlling blood sugar, these drugs also reduce weight, so pharmaceutical companies have developed special formulations to help patients lose weight.
In 2022, a Phase 3 randomized controlled clinical trial showed that ticetide resulted in a 20% reduction in body weight over 72 weeks. The findings prompted the U.S. Food and Drug Administration (fda) last month to approve the drug, marketed under the trade name Zepbound, for weight loss in people with a body mass index (BMI) of 30 or higher, or a BMI of 27 or higher, who also have health problems such as high cholesterol or high blood pressure.
While the initial effects were significant, the researchers were unsure whether the weight loss would persist after aggressive treatment. To find out, they conducted the SURMOUNT-4 trial from March 2021 to May 2023 at 70 sites in Argentina, Brazil, Taiwan and the United States. Participants who took the maximum tolerated dose of tisiparatide for 36 weeks were expected to lose 20.9% of their body weight and to improve their blood pressure, blood glucose markers and lipid levels.
The 670 eligible participants were then randomly assigned to either continue using tisiparatide for one year (52 weeks) or switch to a placebo. Those who continued to take tisiparatide lost 5.5 percent of their body weight, while the placebo group only regained 14 percent.
While the placebo group still weighed nearly 10 percent less than their starting weight, improvements in cardiometabolic risk factors were reversed. Compared with placebo, tisiparatide was associated with significant improvements in BMI, lipid levels, diabetes markers, and blood pressure.
"Those who took the placebo regained about half of their weight," said Dr. Aronne, who is also an internist at NewYork-Presbyterian/Weill Cornell Medical Center who specializes in diabetes and obesity. "And those who stayed on the medication lost another 5 percent, so they lost about 25 percent of their overall body weight."
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The findings suggest that people may need to continue taking tisiparatide to lose weight. "If you stop taking the medication, the weight will come back. It's definitely going to happen, "Dr. Aronne said. But that's not surprising. "Obesity is a chronic disease, like diabetes or high blood pressure. So, long-term treatment is necessary."
The researchers note that they did not assess the impact of intensive behavioral therapy on maintaining weight loss, which may prevent weight regain after stopping the drug.
Ticetide mimics natural hormones and promotes satiety
Tisiparatide works by mimicking the GLP-1 and GIP hormones that the gut naturally secretes after a meal, thereby boosting insulin secretion. It also reduces appetite by slowing down the time it takes for the stomach to empty and interacting with regions of the brain containing GLP-1 receptors to signal fullness.
"Instead of counting calories, the drug helps people eat less because it signals to the brain that you're full," Dr. Aronne said. "The dual mechanism of action helps overcome the platework seen at some point and produces additional weight loss."
Because the drug mimics the hormones produced in the gastrointestinal system, side effects are often nausea, vomiting, diarrhea, or constipation and go away over time. Almost no one dropped out of the study because of side effects.
"People feel much better after losing this kind of weight, so they are very enthusiastic about these treatments." But they should also be aware that it may require them to take this drug for a long time, "Dr. Aronne said. Further research is needed to assess the long-term risks and benefits associated with these drugs, especially given their potential for lifetime use.
